This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. This research focus is centered on glycocoproeins that play key roles in numerous biological functions. More precisely, we are investigating the fragmentation of these biomolecules employing high resolution mass spectrometers such as SolariX 12T FTMS (Bruker) and LTQ-Orbitrap (Thermo-Fisher) equipped with numerous activation modes: collision-induced dissociation (CID), infrared-multiphoton dissociation (IRMPD), electron-capture dissociation (ECD) or electron-transfer dissociation (ETD). Because of the activation mode diversity and high resolution detection, our tandem mass spectrometry experiments provide crucial information for detailed characterization of proteins and glycoproteins that should lead to a better understanding of how development, disease and aging-related modifications to the basic structures of these molecules affect their localization, actions and interactions. Results to date indicate that top-down ETD and ECD MS/MS spectra of intact glycoproteins show minimal loss of either monosaccharides or whole glycan chains. Preliminary esults were presented at the US HUPO meeting in march 2011 and more extensive results will be presented at the 2011 ASMS meeting. A manuscript is being readied for submission.